Towards a new treatment for arterial thrombosis

Cardiovascular disease (CVD) is the leading cause of death in developed countries, surpassing cancer. Stroke, myocardial infarction or pulmonary embolism are due to thrombosis, i.e. blood clots that form inside blood vessels and thus, block the blood flow. Scientists from the University of Liège (GIGA), in collaboration with an American laboratory, may have discovered a novel anti-thrombotic strategy to prevent or treat these life threatening diseases. They have recently published their work in Circulation, the Journal of the American Heart Association (AHA) (1).
The GIGA scientists have identified a protein called DUSP3 as a potential anti-thrombotic drug target. This protein is produced inside platelets and plays a positive role in platelet activation, causing blood clot formation. Finding pharmacological agents to block this protein activity will probably be a starting point for the discovery of new anti-thrombotic drugs.

thrombosisIntuitively, thrombosis is an easy phenomenon to understand: a clot that forms in an artery or a vein that prevents blood flow. It is similar to what happens when there is an accident on a motorway: three lanes are obstructed and hundreds of vehicles are stopped. When a blockage occurs somewhere in the circulatory system, the extent of the resulting damage depends on whether the affected “motorway” supplies the entire country or a small country road leading to a dead end.

We undoubtedly have frequent small asymptomatic blockages which occur somewhere in our circulatory system with no detrimental effects on our health. However, these blockages can be problematic, for example, when they occur in leg veins leading to the so-called “phlebitis”. Fifty per cent of cases of phlebitis are asymptomatic. The other fifty per cent of cases may include symptoms of pain, redness or swelling of the affected leg.  Pulmonary embolism is a possible complication of phlebitis when the blood clot is released into the blood stream and migrates to the heart and pulmonary circulation. This can result in breathlessness, chest pain and palpitations. Pulmonary embolism can lead to death. The risk factors of phlebitis can be temporary: long immobilization, an orthopedic surgical intervention, a plane journey or a pregnancy but they can also be permanent: ageing, obesity, heart failure, cancer etc.

The most frequent arterial thrombosis is the one affecting the coronary arteries leading to myocardial infarction. If the thrombus/clot reaches an artery that supplies the brain, it can cause a cerebrovascular accident (CVA) or stroke, which consists of a sudden interruption in the blood supply to part of the brain. Deprived of oxygen, brain cells die leading to permanent brain damage with serious consequences resulting in a vegetative state, physical or mental handicap etc.

For sure, the pathological process leading to arterial thrombosis is a long and insidious phenomenon. It is due to atherosclerosis, i.e. development of cholesterol-rich atheromatous plaques in the arterial wall. Thrombosis occurs at late stages, when a vulnerable plaque suddenly ruptures. Risk factors for atherosclerosis are hypertension, bad cholesterol, diabetes, smoking or alcohol abuse, in addition to aging.

(1) Dual-specificity Phsophatase 3 Deficiency or Inhibition Limits Platelet Activation and Arterial Thrombosis.

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